The goal of the proposed research program is to discover and begin development of novel compounds as potential antiviral and anticancer drugs. With SBIR Phase I funding, two related in vitro drug screening assays were developed. These assays are based on the activity of the cellular enzyme PKR (Protein Kinase RNA-Activated). PKR is induced by interferon and activated by double-stranded RNA. Active PKR inhibits translation. By inhibiting translation the cell stops viral replication since viruses are dependent on host cell translation. Some viruses (e.g. adenovirus, influenza virus, HIV) have evolved mechanisms to inhibit PKR. In addition to its antiviral effects, PKR may also function as a tumor suppressor. Activators of PKR may be useful antitumorigenic compounds, since activation could inhibit translation, leading to growth suppression of the tumor. With SBIR Phase II funding, RiboGene will utilize the assays developed In Phase l for large-scale screening to identify compounds with potential antiviral and anticancer activities. Samples identified during screening will be tested further, both in tissue culture systems and in animal models. Promising lead compounds discovered in Phase II they will be further developed through preclinical and clinical trials during Phase III. PROPOSED COMMERCIAL APPLICATION: This research will result in the identification of novel antiviral and anticancer drugs.